pH variation impacts molecular pathways associated with somatic cell reprogramming and differentiation of pluripotent stem cells

Abstract

Rationale: The study of somatic cell reprogramming and cell differentiation is essential for the application of recent techniques in regenerative medicine. It is, specifically, necessary to determine the appropriate conditions required for the induction of reprogramming and cell differentiation. Methods: Based on a comprehensive literature review, the effects of pH fluctuation on alternative splicing, mitochondria, plasma membrane, and phase separation, in several cell types are discussed. Additionally, the associated molecular pathways important for the induction of differentiation and reprogramming are reviewed. Results: While cells change their state, several factors such as cytokines and physical parameters affect cellular reprogramming and differentiation. As the extracellular and intracellular pH affects biophysical phenomena in a cell, the effects of pH fluctuation can ultimately decide the cell fate through molecular pathways. Though few studies have reported on the direct effects of culture pH on cell state, there is substantial information on the pathways related to stem cell differentiation and somatic cell reprogramming that can be stimulated by environmental pH. Conclusion: Environmental pH fluctuations may decide cell fate through the molecular pathways associated with somatic cell reprogramming and cell differentiation.